Capacity building on GMP to promote domestic pharmaceutical manufacturing Suggest a more concise title - example on this slide. I do not think it is necessary to specify "Overview" General notes on presentation – since PQM is prominent on every slide, it is not necessary to repeat it over-often in the body of the slide text or headings. I realize the (a) this is not a training and (b) this is needed right away, so I offer the following for the next revision: There are some very densely packed slides. I would recommend cutting down the verbiage per slide to have only the minimal major points, so that the focus of the audience will be on the strength of your presentation of the information. Otherwise, people are going to be reading while you’re speaking, and they will miss the full impact of your message. The graphics need work. At a minimum, they should have the same color scheme. Some are slightly distorted and/or of lower resolution than optimal. Gabriel K. Kaddu Senior GMP Specialist Promoting the Quality of Medicines Program U.S. Pharmacopeial Convention

EAC Pharmaceutical manufacturing plan of Action Outline EAC Pharmaceutical manufacturing plan of Action Introduction to the Promoting the Quality of Medicines (PQM) Program Global medicines quality-assurance and WHO prequalification process Overview of PQM technical assistance PQM technical assistance results and public health impact Conclusion

EAC Pharmaceutical Manufacturing Plan of Action (EAC-RPMPoA ) - Goal The overall goal of the EAC Regional Pharmaceutical Manufacturing Plan of Action (EACRPMPoA) is to ensure availability and access to affordable, high-quality and efficacious essential medicines for the treatment of priority communicable and non-communicable diseases, including HIV/AIDS, Malaria, Tuberculosis (TB), Diabetes, Cardiovascular Diseases, Chronic Respiratory Diseases and Cancers as well as various Neglected Tropical Diseases (NTDs) in the region. The main objective is to improve the capacity of the EAC region to sustainably and competitively produce quality essential medicines for local use and export.

Promoting the Quality of Medicines in Developing Countries (PQM) PQM serves as a primary mechanism to help USAID- supported countries strengthen their quality assurance (QA) and quality control (QC) systems to better ensure the quality of medicines that reach patients. PQM provides Technical Assistance to: Manufacturers National Medicine Regulatory Authorities (NMRAs) National Quality Control Laboratories (NQCLs) Treatment failure, increased morbidity, development of drug resistance, and wasted resources: The effects of substandard and counterfeit medicines are devastating. In developing countries, where resources to combat such medicines are limited, their impact is hardest felt.

Background Since 1992, USP has worked cooperatively with the United States Agency for International Development (USAID) to help developing countries address critical issues related to poor quality medicines. This partnership operated as the Drug Quality and Information (DQI) program until 2009, when, to better meet growing global needs, USAID awarded USP a five- year, $35 million cooperative agreement to establish a new, expanded program—Promoting the Quality of Medicines (PQM). In 2013, USAID extended the PQM program for five years (through September 2019), increased its funding from $35 million to $110 million, and expanded the geographical reach of the program.

USP–USAID Cooperative Agreements Rational Pharmaceutical Management (RPM) Worldwide 1992–2000 RPM Russia/NIS 1993–2000 USP Drug Quality and Information Program (USP DQI) 2000–2005 DQI Extended 2005–2010 Promoting the Quality of Medicines (PQM) 2009–2014 PQM Extended 2014-2019 Changed from 000,000 to M -- from a distance the multiple zeroes can be hard to see and distracting $10 M $110 M $35 M

Program Objectives Prom oting the Qualit y of Medic ines 2009- 2019 Build capa city and stren gthe n QA/ QC syste ms Help incre ase supp ly of QA medi cines Combat falsified, substandard and unapproved medicines Provi de tech nical lead ershi p Strengthening medicines quality assurance systems, e.g. national quality control labs and medicine regulatory authorities Improving the supply of quality-assured medicines, e.g. supporting WHO prequalification, assisting select manufacturers in GMP compliance and dossier preparation Combating substandard and counterfeit medicines, e.g. through post-marketing surveillance of medicine quality, international collaborations Providing technical assistance and global advocacy, e.g. through field-based research (cf. Quality of Antimalarials in Sub-Saharan Africa (QAMSA) Report), technical evaluation of screening tools Developing public product standards, e.g. pharmacopeial monographs for procurement purposes and for the analysis of medicine quality 8

Global Quality Assurance Mechanism for Medicines Procurement Countries, NGOs, partners, procurement agencies are advised to procure ONLY finished pharmaceutical products (FPPs) that meet the following standards: Approved by the WHO Prequalification Program (WHO PQP) or Time-limited advice by an Expert Review Panel (ERP) Authorized by a Stringent Regulatory Authority (SRA) Why is this important: So that: Apply unified standards for assessing quality, safety and efficacy (Q, S & E) Comprehensively evaluate the Q, S & E of medicinal products and APIs, based on information submitted by the manufacturers ….. and inspection of the corresponding manufacturing and clinical sites.

Chemistry, Manufacturing and Controls (CMCs) and Good Manufacturing Practices (GMPs)

Technical Assistance to Manufacturers Top-notch GMP experts with EU, US FDA, and WHO PQ experiences Extensive knowledge of the API and FPP landscape of the global public health market Strong relationship with manufacturers and CROs Intense hands-on and results-driven technical assistance, until product is approved

Technical Assistance to Manufacturers Provide hands-on training and consultation to manufacturers on process/product development and manufacturing Provide guidance on API process development and scale-up Provide guidance on drug product development and scale-up Troubleshoot API and formulation process issues Support to product dossier Assist in the compilation of dossiers according to CTD format  CTD Module 3 (Quality) and Module 5 (BE/Clinical) Direct critical research to fulfill dossier requirements Support to facility GMP/GCP Compliance Manufacturers – GMP compliance Contract research organization – GCP/GLP compliance Continuous follow-up and support until product approval

Dossier: Common Technical Document Format Multisource (generic) products CMC/cGMPs BA/BE

Major challenge: BA/BE Studies High cost of BE studies and surge in notice of concern make this a key area of need PQM provides technical support to regulators and CROs to conduct BA/BE studies, according to GCPs and GLPs Training of regulators and CROs BA/BE guidance and procedures GCP Support - Protocol development, study conduct, monitoring, termination, QMS audit, PK/Stats analysis, reporting and documentation GLPs (ISO/IEC 15189,17034) Reference (R) Test (T)

GMP Technical Assistance Workflow Manufacturers identified through EOI, PQM training workshops, or referral by external partners PQM conducts screening of manufacturers using questionnaire and GMP walk-through PQM conducts gap analysis (Dossier and Facility GMPs) PQM assists manufactures to compile product dossier according to CTD format PQM verifies dossier prior to final submission and conduct pre-inspection mock audit (Support Continues Until Product Approval) PQM issues gap analysis report, work with manufacturers to develop CAPA plan, and complete CAPAs PQM assists pharmaceutical manufacturers and regulator in low- and middle-income countries in achieving compliance with regulatory requirements of stringent markets, such the United States, Europe, and WHO Prequalification program. Medicines regulatory authorities and manufacturers are trained in all aspect of dossier and cGMPs. By obtaining the approval of a stringent regulatory authority, quality-assured priority medicines become available to the public health market.

PQM Technical Assistance Results ─ WHO PQ, USFDA, EU 1 Cycloserine FPP Dong-A Pharma WHO PQ 2012 2 Zinc Sulfate FPP Lab Pharma Rodael 3 Streptomycin API  Shengxue Pharma Spanish RA 2013 4 Isoniazid API Second Pharma 5 Capreomycin API NCPC Pharma 2014 6 Hisun Pharma 7 Levofloxacin API  Langhua Pharma 8 Mebendazole API Yabang Phama CEP 9 Azithromycin FPP HEC Pharma 10 Capreomycin FPP 2015 11 Moxifloxacin API 12 Chi Pharma UNICEF 13 Kanamycin FPP Interpharma/SHP Global Fund ERP 14 Kanamycin API ( non-sterile) Fuzhou Fuxin Pharma USFDA 15 16 Kanamycin API (Sterile) 2016 17 Changzhou Yabang Pharma 18 Cycloserine API 19 Streptomycin API NCPC Huasheng Pharma 20 Rifampicin API Shenyang Antibiotic Manufacturer  

PQM Portfolio ─ Current USAID Priority Medicines by Disease Program Tuberculosis Maternal, Newborn, Child Health Neglected Tropical Disease  High Priority: Kanamycin Sulfate API, Clofazimine API, Clofazimine 100mg capsules Linezolid API, Linezolid 600 mg coated (scored) Gatifloxacin API, Gatifloxacin 200mg Tablet Gatifloxacin 400mg Tablet Moxifloxacin API Rifapentine FDC (Rifapentine with INH) Pediatric first line fixed-dosed combination (preferably dispersible or crushable tablets): Rifampicin(R) 75 mg/ Isoniazid 50mg / Pyrazinamide 150mg Rifampicin(R) 75 mg/ Isoniazid 50mg   Medium Priority Capreomycin API Terizidone API Terizidone, tablet/capsule 250 mg Terizidone, tablet/capsule 300 mg Rifampicin API High Priority: Amoxicillin 250 mg scored DT 7.1% Chlorhexidine digluconate (4%) gel 7.1% Chlorhexidine digluconate (4%) sol Medium Priority: Magnesium sulfate injection 500 mg/ml, in 2-ml and 10 ml ampoule Gentamicin injection 10mg/ml and 40 mg/ml, in 2-ml vial Medium - low Priority: Oxytocin, injection 10 IU, 1-ml Low Priority: Misoprostol 200-ug tablet Betamethasone injection 5.7 mg/ml (betamethasone sodium phosphate 3.9 mg/ml solution, or betamethasone acetate 3 mg aqueous suspension) Dexamethasone injection 4 mg injection (4 mg dexamethasone disodium phosphate in 1-ml ampoule) Praziquantel API Praziquantel 600mg Tablet Mebendazole API Mebendazole 500mg tabet (chewable*) Albendazole API Albendazole 400mg tablet (chewable*, preferably scored)

Conclusion PQM is a major contributor to capacity building technical assistance for regulators and manufacturers PQM assists manufacturers shorten their timeline for WHO PQ, through hands-on assistance on product development, dossier preparation, cGMP and GCPs With PQM technical assistance, manufacturers often pass the WHO PQ inspection on the first attempt Through PQM capacity building activities, PQM ensures availability to quality-assured medicines